AB0425 WHAT DOES IT MEAN TO BE A DUAL BICLA AND SRI(4) RESPONDER? A POOLED ANALYSIS OF TWO PHASE 3 TRIALS IN PATIENTS WITH SLE
Authors: I. N. Bruce, K. Psachoulia, E. Maho, D. Isenberg, R. van Vollenhoven, R. Furie, E. F. Morand, C. Lindholm, M. Hultquist, R. Tummala
Journal: Annals of the Rheumatic Diseases (2022)

Background The BILAG–based Composite Lupus Assessment (BICLA) and SLE Responder Index ≥4 (SRI[4], based on SLEDAI-2K) are validated composite global measures of clinically meaningful improvement in SLE disease activity. BICLA and SRI(4) responses were endpoints in the phase 2b MUSE and phase 3 TULIP-1/-2 trials. 1–3 In a post hoc analysis, more patients met both the BICLA and SRI(4) response criteria at Week 52 (dual responders) with anifrolumab 300 mg vs placebo across trials (MUSE: 48.5% vs 19.9%; TULIP-1: 42.2% vs 27.9%; TULIP-2: 43.4% vs 26.4%; all nominal P &lt;0.01). 4 Whereas the clinical benefit of BICLA responses alone have been characterized, 5 the added benefit of dual BICLA/SRI(4) responses remains unknown. Objectives To understand the clinical benefits (SLE clinical assessments, patient-reported outcomes [PROs], and healthcare utilization) of having a dual BICLA/SRI(4) response vs a response for just one endpoint or nonresponse for both, irrespective of treatment assignment. Methods This was a post hoc analysis of pooled data from the randomized, 52-week, double-blind TULIP-1 ( NCT02446912 ) and TULIP-2 ( NCT02446899 ) trials in which patients with moderate to severe SLE despite standard therapy received intravenous anifrolumab (150/300 mg) or placebo every 4 weeks for 48 weeks. 1,2 Patients were categorized as dual responders (met both BICLA and SRI[4] response criteria at Week 52), single responders (met one of either BICLA or SRI[4] response criteria), or dual nonresponders (did not meet either response criteria). SLE clinical assessments, PROs, and healthcare utilization through Week 52 were evaluated for each group. Statistical comparisons were conducted for dual responders vs single responders and dual nonresponders. Results Patient demographics and baseline characteristics were generally balanced across dual responders (n=288), single responders (n=122), and dual nonresponders (n=409). At Week 52, dual responders had greater improvements in SLE-related measures compared with dual nonresponders across all evaluated clinical, PRO, and healthcare utilization outcomes (Figure , A–E). Compared with single responders, dual responders had a significantly greater mean change from baseline in SLEDAI-2K score (−8.2 vs −5.1; nominal P &lt;0.0001), PGA score (−1.3 vs −0.9; nominal P &lt;0.0001), and swollen joint counts (−6.2 vs −4.5; nominal P &lt;0.0001) ( Panel A ); there was also a numerically greater proportion with ≥50% reduction in CLASI-A score (91% vs 76%; nominal P =0.078) ( Panel B ). Dual responders had a greater mean reduction in baseline oral glucocorticoid (GC) daily dose (−5.6 vs −3.4; nominal P =0.006) vs single responders ( Panel A ). For PROs, compared with single responders, dual responders had a greater mean change in baseline PtGA score (−17.7 vs −8.6; nominal P =0.001), and a higher proportion had clinically meaningful improvements from baseline to Week 52 in fatigue (FACIT-F; 56% vs 43%; nominal P =0.014) and SF-36 physical component scores (60% vs 34%; nominal P &lt;0.0001) ( Panel C–D ). Healthcare utilization (ED visits and hospitalizations) was lower in dual responders vs single responders; however, this comparison did not reach nominal significance (nominal P =0.462 and 0.311, respectively) ( Panel E ). Conclusion Patients with SLE with dual responses in two validated outcome measures have significantly better outcomes across a range of clinical, PRO, and healthcare utilization measures compared with dual nonresponders. The higher degree of improvement in disease activity, especially in arthritis, and the greater reduction in oral GC dose compared with single responders is reflected in improved patient well-being, physical functioning, and fatigue. Being a dual responder offers a profound and clinically meaningful outcome for both the clinician and patient. References [1]Furie R. Lancet Rheumatol . 2019;1:e208–19. [2]Morand EF. N Engl J Med . 2020;382:211–21. [3]Furie R. Arthritis Rheumatol. 2017;69:376–86. [4]Isenberg D. Ann Rheum Dis. 2021;80:586–7. [5]Furie R. Arthritis Rheumatol. 2021;73:2059–68. Acknowledgements Writing assistance was provided by Matilda Shackley of JK Associates Inc., part of Fishawack Health. This study was sponsored by AstraZeneca. Disclosure of Interests Ian N. Bruce Speakers bureau: GSK, UCB, Astra Zeneca, Consultant of: AstraZeneca, GSK, UCB, Aurinia, Eli Lilly, BMS, Grant/research support from: GSK, Janssen, Konstantina Psachoulia Shareholder of: AstraZeneca, Employee of: AstraZeneca, Emmanuelle Maho Employee of: AstraZeneca, David Isenberg Consultant of: AstraZeneca, Amgen, Servier, Eli Lilly, UCB, Merck Serono, Ronald van Vollenhoven Speakers bureau: AbbVie, Galapagos, GSK, Janssen, Pfizer, R-Pharma, UCB, Consultant of: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer, UCB, Grant/research support from: MSD, Pfizer, Roche, BMS, GSK, UCB, Richard Furie Speakers bureau: AstraZeneca, Genentech, Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Eric F. Morand Speakers bureau: GSK, Novartis, Paid instructor for: AstraZeneca, Biogen, Eli Lilly, Consultant of: AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, Servier, Grant/research support from: Abbvie, AstraZeneca, Bristol Myers Squibb, GSK, Janssen, Catharina Lindholm Employee of: AstraZeneca, Micki Hultquist Shareholder of: AstraZeneca, J&amp;J, Employee of: AstraZeneca, Raj Tummala Shareholder of: AstraZeneca, Employee of: AstraZeneca